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Meet the Community: Jing Yu
Interview by Charlie Schmidt
Q: What got you interested in developmental biology? A: My earliest interests were in understanding how “naïve” cells differentiate into specialized cells to form an orderly structure. Organogenesis seemed like a good area for my research. This process starts with a small number of cells that don’t have differentiated structures; they interact with each other, they receive signals from other cells, and in the end they make these beautiful complex structures of organs. So, I decided to focus on organogenesis, and once I had made this decision, the next thing was to pick an organ and a model system. Q: And you chose the kidney. Why? A: People ask me that. Why the kidney and not the heart or the brain? I chose the kidney because it gave me the liberty of addressing many different aspects of development in a single organ. For instance, you can study mesenchymal-epithelial interactions, which are a common theme in most organ formations. Also, the formation of the kidney involves branching morphogenesis, which is common to the lung, blood vessels, salivary glands, mammary glands and other organs. Then there’s a more practical side of wanting to study the kidney: On one hand, the field is building up genetic tools; and on the other, one can isolate kidney tissues from the embryo, culture them, and manipulate them in vivo. These two approaches are complimentary, and allow you to investigate kidney development and questions of general development in depth. Q: So, it was your interest in kidney development that guided you towards Andy McMahon’s laboratory? A: Yes. He’s published some key findings in kidney development and then I have to say that his lab is one of the best in mouse genetics. So, I think this is the place to study kidney development using genetic approaches. Q: Your work in the lab produced a paper about a signaling molecule called sonic hedgehog and its role in kidney development. What can you tell us about that? A: Well, we were interested in the developmental role of epithelial cells in the ureteric bud [an embryonic tissue that gives rise to portions of the kidney]. Most people focus on the tip of the ureteric bud, but the trunk of the epithelium [which forms the collecting duct system of the kidney] is pretty much ignored. We found that sonic hedgehog is expressed in that trunk epithelium and that it signals out to surrounding mesenchymal cells. So, this is a case of epithelial-mesenchymal interaction, in which a key link is sonic hedgehog. The importance of the work was that it shows this population of epithelial cells plays an active role in development. We also found that sonic hedgehog regulates the timing and pattern of differentiation of smooth muscle in the kidney. I identified a small population of mesenchymal cells that in mutant kidneys are kept from differentiating into smooth muscle. Again, sonic hedgehog was involved. My hypothesis – and I need to find evidence for this – is that these mesenchymal cells are smooth muscle progenitors that could be coaxed to differentiate into smooth muscle cells later on. Q: Then they may have some clinical uses, correct? A: There are kidney diseases, hydroureter and hydronephrosis, that occur when smooth muscle doesn’t develop correctly. You don’t have the force to push urine down to the bladder so it accumulates and backflows into the kidney. This affects kidney function. If we can coax these progenitor cells to form smooth muscle, it could lead to a cure. But this is really long-term research here. Q: What about your research with this Merck fellowship? A: Yes, that’s a bit of a switch from my smooth muscle project. The Merck fellowship funds an siRNA [small interfering RNA] approach I’ve been developing. This is crucial for a large-scale screen I’ve been doing: I’m screening all the transcription factors in the mouse genome for genes that have specific expression patterns in the developing kidney. This will provide everyone in the kidney field with genetic markers that identify specific populations of cells. We are looking at these genes’ distribution in the kidney and have already identified about 200 genes that have specific expression patterns in the kidney.
A: Yes. The traditional way to assess gene function is to make knockout mice. But doing that for all 200 genes would take quite a long time, if not forever, so we need to look for an alternative, faster approach. That’s how this siRNA project came into the picture. It’s much faster than traditional knockouts and is less laborious. Q: How do you like working in the McMahon laboratory? A: Well, Andy’s lab has a group of very smart people. We have really helpful discussions in the lab all the time. I find that very important to my research. And Andy is very knowledgeable. The working environment is good. Q: How have the facilities and resources helped your research? A: One really good thing here is the Bauer Center for Genomic Research. That facility has a lot of cutting edge equipment. I’ve used some for my own research. That’s one thing that’s really nice about this place: You have access to these great instruments. Q: Has your progress been limited by anything here at MCB? Are there limitations you find challenging? A: Harvard is a challenging place. Everyone here is so good at what they do, you feel that you have to do very well. That can be stressful. I think some pressure from the outside is a good thing, but sometimes it makes it hard to be positive. In general, I think if you want to do good science, this is the place to be. You can really benefit from the people and the facilities in this department.
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